Cultured rat cardiac myocytes have been used as a model to study the possible role of oxidative stress in the cardiotoxicity induced by anthracycline anti-cancer drugs. Changes in the levels of oxidized glutathione levels (GSSG) inside the cell, leakage of reduced glutathione (GSH) and glutathione oxidized (GSSG) from the cells were mainly used as a parameter of oxidative stress. Adriamycin and daunomycin caused a dose and time dependent increase in leakage of glutathione. About 70 to 80% of the glutathione that leaked out of cells was found to be in the reduced form. A selective inhibitor of GSH reductase, bis-chloro ethyl nitroso urea (BCNU) markedly potentiated the daunomycin induced toxicity. 4' -Deoxyadriamycin, which has been shown not to form free radicals that are prerequisites for oxidative stress, also caused a time and dose dependent leakage of GSH without much change in GSSG in the cells. Calcium Ionophore A2318, which does not form any free radicals, also caused a time dependent increase in leakage of GSH from cells without affecting the intracellular GSSG levels.